THE ENDOTHELIUM MEDIATES A NITRIC OXIDE-INDEPENDENT HYPERPOLARIZATIONAND RELAXATION IN THE RAT HEPATIC-ARTERY

The rat hepatic artery responds to acetylcholine (ACh) with an endothe lium-dependent relaxation, which is unaffected by nitric oxide (NO) sy nthase and cyclooxygenase inhibition. The purpose of this study was to investigate whether the NO-independent relaxation is caused by hyperp olarization of the smooth muscle cells. In vessels with endothelium AC h induced a hyperpolarization in the presence of 0.3 mM N omega-nitro- L-arginine (L-NOARG) and 10 mu M indomethacin. The hyperpolarization, which slowly decayed after an initial maximum, generally lasted for at least 20 min. ACh in contrast to levcromakalim failed to hyperpolariz e the smooth muscle cells in endothelium-denuded vessels. In vessels c ontracted by phenylephrine (PhE) ACh caused a concentration-dependent hyperpolarization and relaxation, and both events occurred over the sa me concentration interval. Curve fitting using the Hill equation showe d a close correlation between the hyperpolarization and the relaxation . Exposure to a 30 mM K+ solution abolished the hyperpolarization and suppressed the relaxation induced by ACh. Nimodipine did not affect th e ACh-induced hyperpolarization, whereas the relaxation induced by ACh and levcromakalim, but not that evoked by the NO donor 3-morpholino-s ydnonimin, were attenuated. Glibenclamide had no effect on the ACh-ind uced hyperpolarization and relaxation, but abolished the corresponding responses to levcromakalim. The results demonstrate a NO-independent hyperpolarization and relaxation in the rat hepatic artery. The hyperp olarization and relaxation were endothelium-dependent, and apparently causally related to each other, since interference with the hyperpolar ization or the subsequent effector pathway inhibited the relaxation.